We are establishing defined molecular, biochemical, and non-invasive magnetic resonance (MR) imaging benchmarks for articular cartilage from animals and humans. Our aim is to demonstrate that engineered cartilage will support viability of and matrix production from mammalian chondrocytes using a young bovine source, establish tissue growth which will be qualitatively similar to that produced from avian cells under comparable conditions, and establish maintenance of the hyaline phenotype. We wish to apply mechanical stimulation of chondrocytes and cartilage by application of pulsed low-intensity ultrasound (PLIUS) so as to increase expression of matrix-related mRNA and corresponding matrix production, the goal being to upregulate repair processes in an animal model of osteoarthritis (OA). Ultimately we wish to establish whether these in vitro and animal model effects will translate into treatment of OA in aging humans;that is, investigate the potential of PLIUS as a disease-modifying intervention in human subjects with early OA. Additional work involves administration of exogenous growth factors to developing tissue, both by itself and in combination with PLIUS.